FOX proteins

FOX (Forkhead box) proteins are a family of transcription factors that play important roles in regulating the expression of genes involved in cell growth, proliferation, differentiation, and longevity. Many FOX proteins are important to embryonic development.[1][2] FOX proteins also have pioneering transcription activity by being able to bind condensed chromatin during cell differentiation processes.[3]

The defining feature of FOX proteins is the forkhead box, a sequence of 80 to 100 amino acids forming a motif that binds to DNA. This forkhead motif is also known as the winged helix due to the butterfly-like appearance of the loops in the protein structure of the domain.[4] Forkhead proteins are a subgroup of the helix-turn-helix class of proteins.

Some FOX genes are downstream targets of the hedgehog signaling pathway, which plays a role in the development of basal cellcarcinomas.
Members of the class O regulate metabolism, cellular proliferation, stress tolerance and possibly lifespan. The activity of FoxO is controlled by post-translational modifications, including phosphorylation, acetylation and ubiquitination.[5]

The founding member and namesake of the FOX family is the fork head transcription factor in Drosophila, discovered by Detlef Weigel and Herbert Jäckle.[6][7] Since then a large number of family members have been discovered, especially in vertebrates. Originally they were given vastly different names (such as HFH, FREAC, and fkh), but in 2000 a unified nomenclature was introduced that grouped the FOX proteins into subclasses (FOXA-FOXS) based on sequence conservation.[8]